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After several members of their family die from arsenic poisoning, Merricat Blackwood lives with her older sister Constance and their ailing uncle Julian in isolation on their New England estate, away from hostile local townspeople. For years, Merricat's magic has seemingly protected the family from harm, but their somewhat peaceful existence is interrupted by the arrival of cousin Charles, who plans to steal the family fortune. Charles' arrival also threatens the dark secret they have been hiding.

In March 2010, it was revealed that Douglas would star in the film, and Rachel McAdams and Saoirse Ronan were also rumored to be attached.[4] On August 9, 2016, Sebastian Stan's casting as Charles Blackwood was announced.[3] That same day, Taissa Farmiga, Alexandra Daddario, Willem Dafoe, and Joanne Crawford were confirmed to star in the film.[5] Farmiga and Daddario were cast in the main roles of protagonist Merricat Blackwood and her sister Constance Blackwood, respectively.[6] On August 11, 2016, Crispin Glover was cast as Uncle Julian Blackwood, replacing Dafoe in the role.[7]Peter O'Meara joined the cast on August 21, in the supporting role of Sam Clarke.[8]